Progress in the treatment of solid tumors with apatinib: a systematic review

Abstract

With the investigation of molecular targets, many agents, such as trastuzumab and ramucirumab, have attained a positive outcome in oncotherapy. Vascular endothelial growth factor (VEGF) is considered a potent factor in angiogenesis and plays an important role in the growth of tumors. Moreover, both VEGF and its receptor are usually excessively expressed in solid tumors and could be hopeful targets for the treatment of neoplasms. Apatinib (YN968D1) is an oral small-molecule tyrosine kinase inhibitor of VEGFR-2. By inhibiting several signaling transduction pathways, it restrains angiogenesis and subsequently controls tumorigenesis. According to current studies, apatinib shows promising application in various solid tumors as a post-second- and post-third-line treatment. It could significantly improve the median overall survival and progression-free survival of patients with tolerated adverse reactions. This paper aims to summarize the recent research on apatinib including the mechanism, pharmacokinetics, trials, adverse reactions, and prospect as a treatment.

Apatinib, a Novel Tyrosine Kinase Inhibitor, Promotes ROS-Dependent Apoptosis and Autophagy via the Nrf2/HO-1 Pathway in Ovarian Cancer Cells

“…Considering the fact that high GCLC or GCLM levels are found in patients with various cancers [40,41] and that the reduction of GSH production by the irreversible GCL inhibitor promotes apoptosis and attenuates cell growth in cancer cells [42], we speculate that apatinib may also function as a ROS inducer by suppressing the VEGFR2-Nrf2 path, leading to decreased GCLC and GCLM levels, resulting in the reduction of GSH. Recent studies have mostly focused on apatinib inhibiting VEGFR2 and its downstream pathway as antiangiogenesis and antitumorigenesis targets [14,43,44] owing to the fact that VEGFR2 expression is upregulated in the vasculature of some tumors compared to the normal vascular system [45][46][47]. For instance, VEGFR2 expression is elevated in osteosarcoma and cervical cancer tissues [15,19].…”

Safety and Efficacy of Apatinib Monotherapy for Unresectable, Metastatic Esophageal Cancer: A Single-Arm, Open-Label, Phase II Study

“…The VEGFR2 is commonly expressed in esophageal cancer tissue and is thought to contribute to tumor angiogenesis and dissemination [11]. Apatinib is a novel inhibitor of angiogenesis that targets the intracellular adenosine triphosphate-binding site of VEGFR2 [12]. Apatinib has shown positive results as a second-or further-line treatment in patients with ESCC [13][14][15][16].…”

Endoglin (CD105) and VEGF as potential angiogenic and dissemination markers for colorectal cancer

“…An increase in VEGF synthesis has been associated with tumor vascularization, metastasis, chemoresistance, and a worse prognosis [11,13]. VEGF and its receptors are usually overexpressed in solid tumors and are promising targets for the treatment of neoplasms [14,15].…”